The Latest and Greatest on USP 797/800 - An Update
Transcript of The Latest and Greatest on USP 797/800 - An Update
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1-27-2019
The Latest and Greatest on USP 797/800 - AnUpdateAlyssa DonadioBaptist Hospital of Miami, [email protected]
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CitationDonadio, Alyssa, "The Latest and Greatest on USP 797/800 - An Update" (2019). All Publications. 3089.https://scholarlycommons.baptisthealth.net/se-all-publications/3089
The Latest and Greatest on USP 797/800 – An Update
Alyssa Donadio, Pharm.D., BCPS
PGY-2 Oncology Pharmacy Resident
Baptist Hospital of Miami
Disclosures
The author of this presentation has no relevant financial or non-financial relationships in the products described and reviewed in this presentation.
Objectives
Review the scope and purpose of USP <797> and USP <800> and identify key differences between the two chapters
Describe proposed changes to USP <797> and USP <800> as well as timelines for implementation
Identify challenges that pharmacies may face in implementing the new standards
USP <797> Scope
Applies to compounded sterile preparations in all settings
Describes conditions and practices to prevent harm from:
Microbial contamination (non-sterility)
Excessive bacterial endotoxins
Variability in the intended strength of ingredients
Unintended physical and chemical contaminants
Ingredients of inappropriate quality in compounded sterile products (CSPs)
USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. 2008.
USP <797> Proposed Major Changes
USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. 2008. https://www.usp.org/sites/default/files/usp/document/our-work/compounding/proposed-revisions-gc-797.pdf
2008 Version Proposed 2019 Update
Three risk levels for CSPs• Low risk: aseptic manipulations
within ISO 5 or better hoods; combining 3 or less sterile products into a single bag/vial
• Medium risk: combining > 3commercial sterile drug products and those requiring complex manipulations
• High risk: non-sterile ingredients, lack effective antimicrobial preservatives, sterile surfaces
Simplified compounded sterile preparation (CSP) microbial risk levels• Category 1 CSPs: shorter
beyond-use date (BUD), may be prepared in an unclassified segregated compounding area (SCA)
• Category 2 CSPs: longer BUD, must be prepared in a cleanroom suite (buffer room with ante-room)
N/A Guidance on use of opened or punctured manufactured products and CSPs
2008 Version Proposed 2019 Update
Section on “readying for administration”
Scope of chapter excludesadministration of medications
Investigation in the event of:•Sterility test failure•Recovery of colony-forming units during environmental monitoring
Emphasis on conducting investigations and implementing corrective actions in specific situations such as:•Media fill failure•Personnel qualification failure •Facility certification failure •Out-of-specification results on lab tests •Quality-control check failures •Complaints indicating CSP quality issue•Adverse events
Radiopharmaceuticals as CSPs Removal of section on radiopharmaceuticals – Refer to General Chapter <825>
USP <797> Proposed Major Changes
USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. 2008. https://www.usp.org/sites/default/files/usp/document/our-work/compounding/proposed-revisions-gc-797.pdf
USP <797> Proposed Major Changes
USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. 2008. https://www.usp.org/sites/default/files/usp/document/our-work/compounding/proposed-revisions-gc-797.pdf
2008 Version Proposed 2019 Update
• Anti-neoplastics shall not be prepared as immediate-use CSPs
• All personnel who compound hazardous drugs shall be fully trained in the storage, handling, and disposal of these drugs –annual verification
• Storage preferably within a containment area such as a negative pressure
• Facilities that prepare a “low volume” of HDs may compound in a non-negative pressure room with “two tiers of containment”
Removal of information related to handling of hazardous drugs –Refer to General Chapter <800>
USP <800> Scope
Purpose:
Describe practice and quality standards for handling hazardous drugs in healthcare settings and help promote patient safety, worker safety, and environmental protection
Applies to all healthcare personnel who handle HD preparations and all entities that store, prepare, transport, or administer HDs
Applies to both sterile and nonsterile products
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Who is at Risk?
http://www.usp.org/sites/default/files/usp/document/our-work/healthcare-quality-safety/800-know-your-exposure-to-hazardous-drugs.pdf
Hazardous Drug DefinitionsNIOSH ASHP
Carcinogenicity Carcinogenicity in animal models, in the patient population, or in both
Teratogenicity or developmental toxicity
Teratogenicity in animal studies or in treated patients
Reproductive toxicity Fertility impairment in animal studies or in treated patients
Organ toxicity at low doses Evidence of serious organ or other toxicity at low doses in animal models or in treated patients
Genotoxicity Genotoxicity (i.e., mutagenicity and clastogenicity in short-term test systems)
Structure and toxicityprofile of new drugs that mimic existing drugs determined by hazardous criteria above
Power LA, Coyne JW. ASHP Guidelines on Handling Hazardous Drugs. Am J Health-Syst Pharm Oct 2018.
History of Hazardous Drug Guidance
1983-84 - ASHP Practice Spotlight: safe handling of cytotoxic drugs
2004 - NIOSH Alert
2006 - ASHP Guidelines on Handling Hazardous Drugs
2008 - USP 797 revision in 2008 to harmonize with NIOSH 2004 alert
2010 - NIOSH list of antineoplastic and hazardous drugs
2016 - USP Chapter 800 Hazardous Drugs—Handling in Healthcare Settings
NIOSH ListNational Institute for Occupational
Safety and Health
3 groups of drugs: Group 1: Antineoplastic drugs
Group 2: Non-antineoplastic drugs that meet one or more of the NIOSH criteria for a hazardous drug
Group 3: Reproductive risk
Updated every 2 years
NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016.
Hazardous Drugs List
Institution-specific HD list must be maintained and reviewed annually
Assessment of new drugs
Classify investigational agents based on mechanism of action
Re-categorization as new toxicologic information becomes available
Consider dosage form
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Exposure Risk Points
http://www.usp.org/sites/default/files/usp/document/our-work/healthcare-quality-safety/800-know-your-exposure-to-hazardous-drugs.pdf
HD Receipt
Receive HD in sealed, impervious plastic wrap
Handle with chemotherapy gloves
Open in neutral or negative-pressure non-sterile area
Immediately deliver toHD storage area
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
HD Storage
HDs must be stored in an externally ventilated, negative-pressure room with at least 12 air changes per hour (ACPH)
Designated hazardous drug sign displayed
Restricted access
Antineoplastic HD requiring further manipulation stored separately
Dedicated storage refrigerator
Sterile and non-sterile HD can be stored together
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
HD Sterile Compounding
Containment Primary Engineering Control(C-PEC)
Externally vented
ISO Class 5 or better air quality
Biological safety cabinet (BSC)• Class II
• Lined with plastic-backed mat
Compounding Aseptic Containment Isolator (CACI)
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Biological safety cabinet (BSC) II
HD Sterile Compounding
Containment Secondary Engineering Control (C-SEC)
Externally vented
ISO Class 7 or better air quality
Negative pressure
HEPA filter• 12 or 30 ACPH
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
HD Sterile Compounding
Closed-System Transfer Devices (CSTD)
HD Non-sterile Compounding
Containment Primary Engineering Control (C-PEC)
Externally vented or redundant HEPA filtered
Biological safety cabinet (BSC) class I or II
CACI
Containment ventilated enclosure (CVE)
Containment SecondaryEngineering Control (C-SEC)
Externally vented
Negative pressure
HEPA filter - 12 ACPH
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Environmental Quality and Control
Environmental wipe studies for HDs shouldbe performed routinely at least every 6 months
Surface wipe sampling should include:
C‐PEC and equipment
Staging or work areas near C‐PEC/pass‐through
Areas adjacent to C-PECs (floors)
Areas outside of buffer room and patient administration areas
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Personal Protective Equipment (PPE)
Protection, reduce exposure to HDs aerosolization and drug residue
Handling all HDs: gloves
Compounding HDs: gowns, gloves, head, hair, and double shoe covers
Double gloves for sterile compounding
Administering injectable HDs: gloves and gowns
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Personal Protective Equipment (PPE)
Spills, cleaning under C-PEC work surface, suspected airborne HD exposure:
Chemical cartridge type respirator or powered air-purifying respirator (PAPR)
Other activities requiring respiratory protection:
N95 respirator
No protection vs. gases/vapors and little protection vs. direct liquid splashes
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Hazard Communication Plan
Institutions must establish policies and procedures for all aspects of HD handling
Elements of the plan: Written plan on how the standard will be implemented
All containers of hazardous chemicals shall be labeled, tagged, or marked with identity of the material and appropriate hazard warnings
Safety Data Sheets (SDS) must be maintained for all hazardous chemical used and accessible to staff
Training program for staff with potential for exposure
Personnel of reproductive capability confirm in writing that they understand risks of handling HDs
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Personnel Training
Training prior to employee independently handling HDs and reassessed annually
Must include:
Overview of the institution’s list of HDs
Review of SOPs related to handling of HDs
Proper use of PPE and equipment/devices
Spill management
Response to known or suspected HD exposure
Proper disposal of HDs
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Labeling/Packaging/Transport
Labeling: HDs must be labeled as such
Packaging: Use containers to maintain physical integrity, stability and sterility during transport
Transport:
Use containers that minimize therisk of breakage/leakage
Never use pneumatic tubesto transport antineoplastic HDs
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
HD Dispensing
HDs not requiring further manipulation may be dispensed without further requirements for containment, unless:
Required by manufacturer
Visual indicators of HD exposure
Segregate equipment used for dispensing activities for HD
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
HD Administration
HDs must be administered safely using protective medical devices and techniques
Appropriate PPE worn when administering HDs and disposed properly
CSTDs must be used for administration of antineoplastic HDs when dosage form allows
Avoid manipulating HD dosage forms when possible
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Deactivating, Decontaminating, Cleaning, Disinfecting
Process Description Agents
DeactivationInactivation of HD compounds
Sodium hypochlorite (Bleach)Peroxide
Decontamination
Physicallyremove
inactivated particles
Sodium hypochlorite (Bleach)PeroxideAlcoholWater
CleaningRemoval of
organic/inorganicmaterial
Germicidal detergent
DisinfectionInhibit/destroy microorganisms
Sterile alcoholDisinfectant
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
HD Spills
Training about proper spill kit use
SOPs required for spill prevention and cleanup procedures (including use of PPE and respirators)
Document circumstances of spill
Immediate medical evaluationfor potentially exposedpersonnel
Non‐employees exposed
should report to ED for evaluationUSP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
HD Disposal Bulk Hazardous Drug Waste
>3% of the capacity of the container
Chemotherapy vials (empty or partially full), syringes, materials used to clean
Trace‐Contaminated Waste
Minimal drug (<3% total capacity)
Gowns, gloves, gauze, masks
May be incinerated at medicalregulated waste facility
Sharps
Needles, ampules, syringes
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Medical Surveillance Program
Should have the following elements:
Baseline assessment of worker’s health and medical history
Estimate of workers HD exposure over time
Monitoring of organ function at risk for toxicity from HD exposure
Follow‐up plan for acute and long‐term
exposure to HDs
USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Old vs. New HD Standards
2008 Version USP <797> USP <800>
Storage preferably within a containment area such as a negative pressure
HDs must be stored in an externally ventilated, negative-pressure room with at least 12 air changes per hour (ACPH)
Facilities that prepare a “low volume” of HDs may compound in a non-negative pressure room with “two tiers of containment”
All facilities that prepare HDs must have a containment secondary engineering control (C-SEC)
•Must be externally vented, physically separated, have appropriate air exchange, and have a negative pressure
USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. 2008. USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
Old vs. New HD Standards
2008 Version USP <797> USP <800>
Only allows low-risk non-HD Compounded Sterile Preparations (CSPs) with 12 hour or less beyond-use date (BUD) to be prepared in an unclassified segregated compounding area (SCA)
Allows low and medium risk HD CSPs to be prepared in an unclassified containment segregated compounding area (C-SCA)
• C-SCA required to have fixed walls, be externally vented with 30 ACPH and have negative pressure
*Note differences in terminology and requirements in the SCA in USP <797> and C-SCA in <800>
USP General Chapter <797> Pharmaceutical Compounding—Sterile Preparations. 2008. USP General Chapter <800> Hazardous Drugs - Handling in Healthcare Settings
USP Timeline for General Chapter Revisions
Potential Challenges
Financial/physical plant
New equipment
Facility design changes
Separation of hazardous/non-hazardous compounding
Storage
Time
Documentation
More frequent environmental sampling
Potential Challenges
Staff training/education
Lack of evidence
Recommendations based on expert panel opinions
Impact on low volume sites
Outpatient clinics, physician offices, etc.
Douglass K, Kastango E, Cantor P. Pharmacy Purchasing and Products. 2017;14(10):16.
2017 USP 797 Compliance Study
Douglass K, Kastango E, Cantor P. Pharmacy Purchasing and Products. 2017;14(10):16.
2017 USP 797 Compliance Study
Douglass K, Kastango E, Cantor P. Pharmacy Purchasing and Products. 2017;14(10):16.
2017 USP 797 Compliance Study
Douglass K, Kastango E, Cantor P. Pharmacy Purchasing and Products. 2017;14(10):16.
2017 USP 797 Compliance Study
2017 USP 797 Compliance Study
Douglass K, Kastango E, Cantor P. Pharmacy Purchasing and Products. 2017;14(10):16.
Self-Assessment
True/False: USP <800> applies only to the compounding of sterile hazardous drugs
True/False: USP <797> and USP <800> updates are anticipated to become official on December 1, 2019
True/False: The most common challenge to achieving USP compliance has been identified to be financial restrictions
Summary
USP 797 sets sterile compounding standards vs. USP 800 sets hazardous drug handling standards
Updated versions will be enforceable December 1, 2019
Institutions should determine readiness to meet standards early
Some standards will require significant investment of time and money
References1. The United States Pharmacopeial Convention. USP general chapter <797>
Pharmaceutical Compounding—Sterile Preparations. 2008. 2. American Society of Health‐System Pharmacists. ASHP Guideline Guidelines on
Handling Hazardous Drugs. Am J Health‐Syst Pharm. 2006;63:1172‐1193.
3. Power LA, Coyne JW. ASHP Guidelines on Handling Hazardous Drugs. American Journal of Health-System Pharmacy Oct 2018, ajhp180564.
4. Chaffee, BW, Armitstead, JA, Benjamin, BE. Guidelines for the safe handling of hazardous drugs: consensus recommendations. Am J Health Syst Pharm. 2010;67(18):1545–1546.
5. NIOSH 2016. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. Connor TH, MacKenzie BA, DeBord DG, Trout DB, O’Callaghan JP. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication Number 2016-161.
6. The United States Pharmacopeial Convention. USP general chapter <800> Hazardous drugs—handling in healthcare settings. 2017. http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare.
7. Douglass K, Kastango E, Cantor P. 2017 USP <797> Compliance Study. Pharmacy Purchasing and Products. 2017;14(10):16.
The Latest and Greatest on USP 797/800 – An Update
Alyssa Donadio, Pharm.D., BCPS
PGY-2 Oncology Pharmacy Resident
Baptist Hospital of Miami